It has become an industry consensus that self-assembled nanoparticles (SAN) are formed by molecular recognition of chemical components in traditional Chinese medicine during the decoction process. The insoluble components in the decoction are mostly in the form of nanoparticles, which can improve the problem of poor water solubility. However, the transfer rate of these insoluble components in the decoction is still very low, which limits the efficacy of the drug. This study aimed to refine the traditional decoction self-assembly phenomenon. The self-assembled nanoparticles were constructed by micro-precipitation method (MP-SAN), and characterized by particle size, zeta potential, stability index and morphology. The formation of MP-SAN and alterations in related physicochemical properties were evaluated using modern spectroscopic and thermal analysis techniques. The quality value transmitting pattern of lignan components within the MP-SAN was assessed via high performance liquid chromatography (HPLC). The MP-SAN showed sphere-like structure with uniform morphology, particle size of (245.3 ± 3.2) nm, polydispersity index (PDI) of (0.13 ± 0.03), zeta potential of (-48.9 ± 5.9) mV and stability index (SI) of (86.05% ± 2.27%). Comprehensive analyses using ultraviolet visible spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and other techniques confirmed molecular recognition between the decoction and ethanol extraction, leading to electron rearrangement under the influence of non-covalent bonding. This resulted in the formation of nanoparticles possessing superior thermal stability. As determined by HPLC, the encapsulation rates of the index components in the MP-SAN were all greater than 75% (dehydrodiconiferyl alcohol: 77.00%; herpetolide A: 78.57%; herpetrione: 94.53%), and the transfer rates were all higher than 65% (dehydrodiconiferyl alcohol: 96.01%; herpetolide A: 67.86%; herpetrione: 65.55%), which were 1.34, 1.38 and 4.81 times compared with those of the traditional decoction. In summary, this study successfully constructed the MP-SAN based on micro-precipitation method to achieve high transfer rate and high encapsulation rate of insoluble components in docoction, which provides a pharmaceutics idea for the efficient utilization of pharmacodynamic substance basis of traditional Chinese medicine.

Objective To observe the clinical efficacy of Modified Tongxie Yaofang(Important Formula for Relieving Diarrhea with Pain)in the treatment of patients with diarrhea-predominant irritable bowel syndrome(IBS-D)with liver-depression and spleen-deficiency syndrome.Methods Sixty patients with IBS-D of liver depression and spleen deficiency type were randomly divided into treatment group and control group,30 patients in each group.The patients in the treatment group were given modified Tongxie Yaofang,and the patients in the control group were given Pivacurium Bromide Tablets(Dicetel).Both groups were treated for a 4-week course of treatment.The changes of traditional Chinese medicine(TCM)syndrome scores,irritable bowel syndrome quality of life(IBS-QOL)scores,Hamilton Anxiety Scale(HAMA)scores of the two groups were observed before and after the treatment.Moreover,the efficacy for overall symptomatic improvement in the two groups was evaluated according to the grading of irritable bowel syndrome symptom severity score(IBS-SSS),and the efficacy for improving single symptom such as abdominal pain and diarrhea as well as the relapse after 4 weeks of drug cessation in the two groups were compared.Results(1)After 4 weeks of treatment,the total effective rate for overall symptomatic improvement in the treatment group was 83.33%(25/30),and that in the control group was 43.33%(13/30).The intergroup comparison(tested by chi-square test)showed that the efficacy for overall symptomatic improvement in the treatment group was significantly superior to that in the control group(P＜0.01).(2)After 4 weeks of treatment,the total effective rate for improving single symptom of abdominal pain and diarrhea in the treatment group was 80.00%(24/30),90.00%(27/30),and that in the control group was 43.33%(13/30),46.67%(14/30),respectively.The intergroup comparison(tested by chi-square test)showed that the efficacy for improving single symptom of abdominal pain and diarrhea in the treatment group was significantly superior to that in the control group(P＜0.01).(3)After 4 weeks of treatment,the TCM syndrome scores,IBS-QOL scores,and HAMA scores of patients in both groups were significantly decreased compared with those before treatment(P＜0.05 or P＜0.01),and the decrease in the treatment group was significantly superior to that in the control group(P＜0.01).(4)After 4 weeks of drug withdrawal,the recurrence rate of the treatment group was 24.00%(6/25),which was significantly lower than that of the control group(61.54%,8/13),and the difference was statistically significant between the two groups(P＜0.05).Conclusion Modified Tongxie Yaofang exerts certain effect in treating patients with IBS-D of liver depression and spleen deficiency type,and the decoction is effective on decreasing the scores of symptoms of abdominal pain and diarrhea as well as TCM syndrome scores,improving the quality of life of the patients,and alleviating the anxiety status of the patients.

Tricuspid regurgitation(TR)is a common heart valve disease.According to the pathogenesis,TR can be divided into primary(organic)and secondary(functional)regurgitation,of which functional TR accounts for more than 90%.Patients with severe TR have poor prognosis and poor drug treatment,and surgery(valvuloplasty)is the main treatment.At present,transcatheter edge-to-edge tricuspid valve repair(T-TEER)has become an essential program of transcatheter treatment for TR,providing minimally invasive treatment for TR patients who cannot undergo surgery or are at high risk of surgery.T-TEER reduces the degree of regurgitation by clamping leaflets,and is currently in the early stage of research and development exploration and clinical validation,mainly for functional TR.T-TEER devices have also made significant progress(TriClip,PASCAL),and Chinese-made novel-designed T-TEER devices are also undergoing clinical trials(DragonFly-TTM,SQ-Kyrin-TTM,NeoBlazarTM).This paper reviews the current applications and research progress of T-TEER.

Heart failure(HF)is the end stage of almost all cardiovascular diseases,including coronary heart disease and structural heart disease.For end-stage HF,medications and cardiac assist devices have limited therapeutic effects,and heart transplantation is associated with donor shortage and immune rejection.Alginate hydrogel has the ability to mechanically support and induce cardiac tissue regeneration and repair.In March 2021,we conducted the world's first transcatheter endocardial alginate-hydrogel implantation in patients with end-stage heart failure,and explored the safety and feasibility of the treatment.Given that patients with heart failure who had undergone cardiac resynchronization therapy defibrillator(CRT-D)were excluded from previous studies,this paper is the first to report a case of transcatheter endocardial alginate-hydrogel implantation in a patient with heart failure who did not respond to CRT-D,with a significant reduction in the number of visits to the doctor and a significant improvement in the quality of life during the post-procedure follow-up,which may expand the indications for the use of this technology.

Abstract: Objective　To construct SARS-CoV-2 receptor binding domain molecular probe for monoclonal memory B cell sorting and obtain RBD specific neutralizing antibodies from peripheral blood mononuclear cells (PBMCs) of COVID-19 convalescents by single-cell sorting. Methods　The SARS-CoV-2 RBD sequence was downloaded from GenBank, and the Avi tag and 6-histidine tags were added at the C-terminal. After codon optimization, it was chemically synthesized, cloned into the pDRVI1.0 vector, expressed after transfection of 293F cells, and biotinylated consequently. RBD-specific B cells were sorted out with this probe1 from the PBMCs of convalescents recovered from COVID-19. After B cells were lysed, the variable regions of heavy chain and light chain were amplified, cloned into the antibody expression vector, and transfected into 293F cells to express the antibody. Then the antibody was purified from the supernatant using protein A column and SARS-CoV-2 pseudovirus was used to test their neutralizing activity. Results　RBD-Avi probe was produced and successfully biotinylated sequentially with an efficiency of 30%-50%. Western blot analysis revealed that the biotinylated probe was recognized by the antibodies purified from COVID-19 convalescent plasma. Using this probe, 7 and 16 RBD-specific memory B cells were successfully isolated from the PBMCs of two convalescent individuals, accounting for 0.24% and 0.17% of the total cell population, respectively. After amplifying the variable regions of antibody heavy and light chains from the lysed B cells, 7 and 12 pairs of antibody heavy-light chains were obtained. A total of 16 antibodies were expressed in the convalescent individuals, and most of the purified antibodies showed neutralizing activity against the pseudovirus, with IC50 values of 6 antibodies below 1 μg/mL. The IC50 values of XJ-A9 and SCF-F1 against the wild-type pseudovirus were 0.07 μg/mL and 0.35 μg/mL, respectively. Conclusion　The SARS-CoV-2 RBD molecular probe constructed in this study has good antigenicity, and the isolated antibodies present neutralizing activity against wild-type SARS-CoV-2 pseudovirus.

With a rapidly aging population， there is a huge potential demand for rehabilitation and assistive products and services. Especially in the global context where greater attention is given to disadvantaged groups， there is a need to cater to the needs of the elderly in terms of rehabilitation and assistive aid to improve their quality of life. Compared with developed countries， China’s rehabilitation aid industry is still in its early stages of development and needs to move away from traditional equipment manufacturing and integrate with intelligent manufacturing to provide more development possibilities and choices. International cooperation is expected to become one of the future research and development directions for rehabilitation aids. Taking typical cities and countries at home and abroad as examples， this paper explores the development of rehabilitation aids， and calls for the cultivation of more rehabilitation aid professionals to help more people in need.

To investigate the effects and mechanism of the combination of Morus alba L. (Sangzhi) alkaloids(SZ-A) and metformin (Met) on glucose metabolism in type 2 diabetic mice, KKAy mice were divided into four groups according to the glucose and lipid indexes: control group (control), Morus alba L. (Sangzhi) alkaloids group (SZ-A, 100 mg·kg^-1), metformin group (Met, 100 mg·kg^-1) and combined administration group (combination, Comb, 100 mg·kg^-1 SZ-A + 100 mg·kg^-1 Met). All groups were administered by gavage once daily for 7 weeks accompanied with monitoring food intake, water intake, body weight as well as glycemia. Additionally, oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and oral sodium pyruvate tolerance test (OPTT) were performed at week 2, week 5, week 6, respectively. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (00004332). We determined the weight and lipid content of liver, and then performed the histopathological analysis after sacrificed. Furthermore, Western blot assay was used to detect the protein levels of key molecules of PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue. Compared to the SZ-A or Met monotherapy group, SZ-A + Met significantly improved the glucose metabolism disorder, which was showed in reduced food intake, water intake, the level of fasting blood glucose, postprandial blood glucose and glycosylated hemoglobin A1c (HbA1c) of KKAy mice, as well as improved glucose tolerance, enhanced insulin sensitivity and inhibited gluconeogenesis. In addition, SZ-A + Met obviously up-regulated the protein expression levels in PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue of KKAy mice. Moreover, the liver lipid accumulation and blood aminotransferase level of KKAy mice in the combined administration group were significantly reduced. Therefore, we concluded that the combination of SZ-A and Met improved glucose metabolism and inhibited the occurrence and development of T2DM via promoting glucose uptake and utilization, suggesting that the combination of SZ-A and Met is a more useful treatment for T2DM.

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

Objective:To provide scientific basis for prevention and control measures of island regions through analyzing the characteristics of malignant tumor incidence and mortality in eastern island areas of China and comparing the data with the national cancer mortality data in the same period. Methods:Using the incidence and mortality data of malignant tumor in Daishan county,Zhoushan collected by the Daishan Center for Disease Control and Prevention(CDC)from 2014 to 2019,which was stratified by gender,the crude incidence rates(CIR)and crude mortality rates(CMR)were calculated,and the top 10 malignant tumors with the highest incidence or mortality rates were then ranked.The Segi's world standard population was used to calculate the age-standardized incidence(ASIR)and age-standardized mortality rate(ASMR).The local data were compared with the national cancer mortality data from 2014 to 2019,and Chi-square test was used to analyze the differences between these two sets of data using the SPSS software.The difference was considered statistically significant when P<0.05. Results:There was a total of 7 305 incidence cases of malignant tumors in Daishan county,Zhoushan from 2014 to 2019.The CIR was 662.39/105 and the ASIR was 306.81/105.Notably,the CIR was the highest in the age group of 75-79 years old.The top 5 malignant tumors with the highest incidence rates were lung cancer(27.15％),gastric cancer(12.76％),liver cancer(10.95％),colorectal cancer(6.92％)and breast cancer(5.42％),whose ASIR were 75.09/105,32.06/105,31.01/105,17.81/105 and 18.36/105,respectively.There was a total of 3 412 mortality cases of malignant tumors in Daishan county,Zhoushan from 2014 to 2019.The CMR was 309.39/105 and the ASMR was 122.73/105.Notably,the CMR was the highest in the age group of 80-85 years old.The top 5 malignant tumors with the highest mortality rates were lung cancer(24.94％),liver cancer(18.64％),gastric cancer(17.00％),colorectal cancer(7.56％)and esophageal cancer(5.72％),whose ASMR were 29.65/105,24.97/105,19.01/105,8.75/105 and 6.60/105,respectively.The total ASMR of malignant tumors in Daishan county,Zhoushan was higher than national total ASMR from 2014 to 2019(100.34/105)(P<0.001).Specifically,the ASMR of gastric cancer,lung cancer and colorectal cancer in Daishan county were significantly higher than national levels(gastric cancer:12.46/105;liver cancer:16.45/105;colorectal cancer:6.63/105)(P<0.01),whereas no significant difference in the ASMR of lung cancer and esophageal cancer between Daishan county and the whole nation(lung cancer:28.06/105;esophageal cancer:7.61/105)was observed. Conclusion:Lung cancer,gastric cancer,liver cancer and colorectal cancer were malignant tumors with higher incidence and mortality rates in Daishan county,Zhoushan from 2014 to 2019.Particularly,the ASMR of gastric cancer,liver cancer and colorectal cancer were significantly higher than the national levels,and these malignant tumors should be considered as the major focus of cancer prevention and control.

Aim To explore the effect of artesunate (ART) on the function of breast cancer cells during the progression of breast cancer and the possible mechanism of action. Methods MCF-7 (30 μmol • L-